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9.
FDA. E 10 Choice of Control Group and Related Issues in Clinical Trials, 2001. Assay Sensitivity Property of a clinical trial that candistinguish an effective treatment from a less effective or ineffective treatment

10.
Superiority TrialsPurpose  To detect a difference between two drugsGoals  Establish new drug is statistically superior to active control (and/or placebo) [Easier]  Establish new drug is clinically superior to active control (and/or placebo) [Harder]

11.
Equivalence Trials Purpose: To confirm the absence of a meaningfuldifference between treatments

13.
What is the PURPOSE of a non-inferiority trial?20% 1. To show the new drug is as good as comparator20% 2. To show the new drug can be better than comparator20% 3. To show the new drug is not unacceptably worse than comparator20% 4. To show the new drug is clinically equivalent to comparator20% 5. To show the new drug performs no better or no worse than comparator

14.
Non-inferiority (NI) TrialsPurpose: To demonstrate that a new drug is not worse than an active comparator by more than a pre-specified amount*NOT: That the two drugs are equivalentNOT: That the new drug isn’t inferior to the active comparator *non-inferiority margin, delta (Δ), 

22.
Historical Evidence of SensitivitySimilarly designed trials in the past regularlydistinguished effective treatments from less effective or ineffective treatmentsBarring this, demonstration of efficacy froma showing of non-inferiority is not possible FDA. E 10 Choice of Control Group and Related Issues in Clinical Trials, 2001.

26.
Data AnalysisUse of BOTH intent-to-treat (ITT) and per protocol (PP) methods of data analysis should be employedGuidance used to suggest PP analysisfor NI due to dilution of effect by ITT Assumptions since proven faulty Stat Med 2005;24(1):1-10.

31.
H0=null hypothesis. Ha = alternative hypothesis; Δ =difference in event rates between new and standard treatments; S=Δ insuperiority trials. E=Δ in equivalence trials; NI =Δ in non-inferiority trials*Testing for non-inferiority is in one direction only — even if superiority exists (dashed arrow), it is not the hypothesis being tested. MJA 2009;190(6):326-330.

40.
What is Biocreep?20% 1. Inability to demonstrate bioequivalence20% 2. Slow crawl towards finding of non- inferiority with ITT analysis20% 3. Temporal reduction of efficacy of drugs using NI trials as evidence20% 4. Process of insertion of biologics into drug pipeline20% 5. The name of the villain from the Hellraiser movies

48.
If this had been an elevator prep (not pitch)• Assay sensitivity and historical evidence is crucial for determination of NI feasibility• Sponsor NI margin selection is contingent upon multiple factors in eyes of FDA• Let guidance by FDA, other bodies, and CONSORT help inform protocol development on front end